Hypoxia‑induced expression of CXCR4 favors trophoblast cell migration and invasion via the activation of HIF‑1α.

The placenta initially develops in a low‑oxygen environment up to week 8‑10 of gestation, and a low oxygen level is a critical factor in the regulation of trophoblast migration and invasion. CXC chemokine receptor 4 (CXCR4) is transcriptionally activated by hypoxia in cancer cells. However, whether CXCR4 is involved in hypoxia‑inducible factor (HIF)‑1α‑dependent trophoblastic migration and invasion in a physiologically hypoxic environment (3% O2) remains to be fully elucidated and requires further investigation. In the present study, the expression of CXCR4 in first‑trimester villi was investigated, as was the response of the trophoblast to hypoxia, and the role of CXCR4 and HIF‑1α in trophoblast migration and invasion. CXCR4 was significantly elevated in the first‑trimester villi compared with normal full‑term placentas. In vitro, the expression of CXCR4 at the mRNA and protein levels was increased in JEG3 cells exposed to 3% O2 in a time‑dependent manner, and the migratory and invasive abilities of the JEG3 cells were upregulated. In addition, CXCR4 knockdown by transfection with CXCR4‑specific small interfering (si)RNA decreased the migration and invasion of JEG3 cells exposed to 3% O2. Furthermore, synthetic siRNA specific for HIF‑1α significantly suppressed the expression of CXCR4 in JEG3 cells exposed to 3% O2, whereas pcDNA‑HIF‑1α significantly increased the expression of CXCR4. These results indicated that the hypoxia‑induced expression of CXCR4 promoted trophoblast cell migration and invasion via the activation of HIF‑1α, which is crucial during placentation.

Pubmed ID: 29786753